Locoregional radiotherapy improves survival outcomes in de novo metastatic nasopharyngeal carcinoma treated with chemoimmunotherapy.

BACKGROUND: We aimed to investigate the efficacy of locoregional radiotherapy (LRRT) in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) receiving chemotherapy combined with anti-programmed cell death receptor-1 monoclonal antibodies (anti-PD-1 mAbs) as first-line treatment and identify optimal candidates for LRRT. MATERIALS AND METHODS: We enrolled patients with dmNPC receiving platinum-based palliative chemotherapy and anti-PD-1 mAbs followed or not followed by LRRT from four centers. The endpoints were progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). We used the inverse probability of treatment weighting (IPTW) to balance the baseline characteristics of the LRRT and non-LRRT groups to minimize selection bias before comparative analyses. Multivariate analyses were carried out using the Cox proportional hazards model. RESULTS: We included 163 patients with dmNPC (median follow-up: 22 months). The median PFS was 20 months, and the ORR was 92.0%; the median OS was not achieved. After IPTW adjustments, patients who received LRRT had a significant survival benefit over those not receiving LRRT (median PFS: 28 versus 15 months, P < 0.001). The Epstein-Barr virus DNA (EBV DNA) level after four to six cycles of anti-PD-1 mAbs [weighted hazard ratio (HR): 2.19, 95% confidence interval (CI) 1.22-3.92, P = 0.008] and LRRT (weighted HR: 0.58, 95% CI 0.34-0.99, P = 0.04) were independent prognostic factors. Patients with undetectable EBV DNA levels after four to six cycles of anti-PD-1 mAbs (early EBV DNA clearance) benefitted from LRRT (HR: 0.41, 95% CI 0.22-0.79, P = 0.008), whereas those with detectable levels did not (HR: 1.30, 95% CI 0.59-2.87, P = 0.51). CONCLUSIONS: Palliative chemotherapy combined with anti-PD-1 mAbs followed by LRRT was associated with improved PFS in patients with dmNPC, especially for patients with early EBV DNA clearance.

[Investigation of hearing loss and speech recognition ability of the elderly and analysis of its high risk factors].

Objective: To investigate the hearing loss and speech disorders in the elderly, to analyze the risk factors of the elderly deafness, as well as to provide reference for the clinical research of the elderly deafness. Methods: From March 2016 to March 2018, 913 elderly people, who were tested for hearing and speech disorders, were examined by a unified questionnaire to investigate the demographic data of the subjects and the related factors of deafness, and the hearing and speech recognition tests were carried out. According to the hearing loss, the hearing impaired group was divided into the hearing impaired group (500, 1 000, 2 000 and 4 000 Hz, the average hearing threshold>25 dBHL) and the non hearing impaired group (the average hearing threshold of the four frequencies ≤25 dBHL), and then the single factor analysis and the unconditional Logistic regression analysis were used. Finally, the risk factors of senile deafness were analyzed. Results: Of the 913 elderly subjects in the survey, 389 (42.61%, 389/913) had no hearing impaired, 345 (37.79%, 345/913) were mild hearing impaired, and 149 (16.32%, 149/913) had moderate hearing loss. Twenty-six patients were severe hearing loss (2.85%, 26/913); 4 patients had severe hearing loss (0.44%, 4/913). Among the 524 hearing-impaired elderly, there were 244 speech-recognition disorders (46.56%, 244/524), of whom 106 were mild hearing-impaired, accounting for 30.72% (106/345), 108 were moderate hearing loss, accounting for 72.48% (108/149), 26 were severe hearing loss, accounting for 100% (26/26), and 4 were the profound hearing loss, accounting for 100% (4/4). Statistical analysis showed that the age, job status, history of hypertension, history of hyperglycemia, and smoking history were independent risk factors for senile hearing loss (P<0.05). Conclusions: High incidences of hearing and speech recognition obstacle are found in health examination for the elderly patients. Noise exposure, age, history of hypertension, high blood sugar, and smoking history are high-risk factors for senile deafness, therefore, prevention and rehabilitation programs are urgent to be developed.

RLN2 regulates in vitro invasion and viability of osteosarcoma MG-63 cells via S100A4/MMP-9 signal.

OBJECTIVE: Relaxin-2 (RLN2) increases cell migration, invasiveness and proliferation in vitro of osteosarcoma cells, but the molecular mechanisms of this action are still unknown. In the present study, we identified S100A4 /MMP-9 signaling as a major mediator of the actions of RLN2 in osteosarcoma cells in vitro. MATERIALS AND METHODS: We have established stable transfectants of osteosarcoma MG-63 cells using small interfering RNA (siRNA) targeting RLN2. The stable transfectants (MG-63/RLN2 siRNA cells) were treated with 20 mM BB94 (a kind of MMP-9 activator) or 100 mM recombinant Human RLN2 (B-29/A-24) for 24 hs or transfected with S100A4 cDNA plasmid for 48 hrs or MMP-9 siRNA for 48 hrs then treated 100 mM recombinant Human RLN2 (B-29/A-24). Western blot assay was used to detect RLN2, S100A4 and MMP-9 expression. Matrigel invasion assay and wound healing assay was used to detect invasion in vitro. MTT was used to detect cell viability. RESULTS: Knockdown of RLN2 using small interfering RNA decreases S100A4 and MMP-9 expression and inhibits invasion and cell viability in vitro. in MG-63 cells. Treatment with 100 mM recombinant Human RLN2 (B-29/A-24) for 24 hrs in MG-63/ RLN2 siRNA cells increases S100A4 and MMP-9 expression, and increases the invasion and cell viability in vitro in MG-63 cells. Transfection with S100A4 cDNA plasmid in MG-63/RLN2 siRNA cells for 48 hrs increases MMP-9 expression, and increase the invasion and cell viability of MG-63/RLN2 siRNA cells. Treatment with 20 mM BB94 (MMP-9 activator) for 24 hrs in MG-63/RLN2 siRNA cells increases MMP-9 expression, and increases the invasion and cell viability in vitro. in MG-63 cells. CONCLUSIONS: Our results indicate that RLN2 regulats cell migration, invasiveness and proliferation of osteosarcoma cells in vitro, which may be mediated through S100A4/MMP-9 signaling.

Antigenic relationship between H1 and H2 of influenza A virus.

Using cloned viruses of proven purity, and by the methods of hemagglutination inhibition, single radial hemolysis, strain-specific complement fixation and neutralization tests we have demonstrated the serological cross reaction between late H1N1 variant (Dutch/56) and H2N2 of influenza A virus with fowl and hamster antisera. Such a cross reaction is not detected with earlier H1N1 variants. Serological crossing covers variants of H2N2 virus isolated from 1957-1966 but in decreasing titers, and disappears with the last variant of H2N2 isolated late in 1967. Analysis with mono-specific antisera or antigens prepared with recombinants reveal that the hemagglutinins of late H1N1 and H2N2 are related, while their neuraminidases are distinct. We have discussed the bearing of such antigenic relationships to previous epidemiological observations on the partial protection of patients convalescent from late H1N1 disease against H2N2 and to the recombination theory for the origin of H2N2 virus.